The sequence of conditions from unstable angina to acute myocardial infarction, to sudden coronary death combined with these is inclusively referred to as Acute Coronary Syndrome (ACS). Each of these occurs when plaques generated due to arteriosclerosis of the coronary arteries supplying nutrients to the myocardium collapse and as a result of thromboses being attached thereon, coronary artery stenosis and blockage occur. Although in modern society the increase in acute coronary syndrome has been plodding along, because most of these are sudden occurrences with no forewarning, sudden death where lifesaving is impossible is a common experience. In addition, even in cases where [the patient] is quickly accepted into a hospital, emergency heart surgery, emergency percutaneous coronary angioplasty (PCI), etc., are often necessary for lifesaving, and the burdens on the medical economy are incalculable.
It has become apparent in recent years that the onset of acute coronary syndrome is caused by the formation of occlusive thromboses continually generated either by the disintegration or erosion of atheromatous arteriosclerosis plaques (non-patent reference 1). Although it has been shown that inflammatory reactions and oxidation stresses within the vascular walls carry an important role in the collapse and erosion of plaques, even among these, increased protease activity and functional impairment of the vascular walls centering on and apotosis (cell death) brought about by LDL (low-specific gravity lipoproteins) which have received the oxidation changes are known the be major factors. LOX-1 (lectin-like oxidized low density lipoprotein receptor-1) is defined as the receptor protein for oxidized LDL (non-patent reference 2).
Although the LOX-1 is normally expressed by cellular-surfaces as a membrane protein in living bodies, it is known for becoming free in the blood as a form of soluble LOX-1 after cleaved at the extracellular domains adjoining the transmembrane part through the action of protease (non-patent reference 3). In addition, because there is a marked rise in blood concentrations of this soluble LOX-1 in the acute phase of acute coronary syndrome, its possibility as a primary diagnostic marker for acute coronary syndrome has been reported (non-patent reference 4).
Therefore, it is said that acute coronary syndrome (ACS) could be prevented beforehand if the volume of soluble LOX-1 present in the blood could be accurately quantitated at an early stage. On the other hand, even though there are reports of antibodies for LOX-1, these are all general writings, and there are currently no reports on immunochemical assay systems such as ELISA, etc., for said purpose, or on high-affinity monoclonal antibodies
(Patent Documentation 1-3.)
[Non-patent Reference 1] Medical Tribune, 1999, Vol. 32, No. 31, p 6.
[Non-patent Reference 2] Nature, 1997, Vol. 386, p 73-77.
[Non-patent Reference 3] Arterioscler. Thromb. Vasc. Biol. 2000, 20 (3), p 715-720
[Non-patent Reference 41 Circulation, 2005, 112 (6), p 812-818
[Patent Reference 1] Laid-open Patent Disclosure No. H9-98787
[Patent Reference 2] Laid-open Patent Disclosure No. 2000-109435.
[Patent Reference 3] Patent Disclosure 2002-510710